Hepatitis C Support Group
Hepatitis C is a blood-borne viral disease which can cause liver inflammation, fibrosis, cirrhosis and liver cancer. The hepatitis C virus (HCV) is spread by blood-to-blood contact with an infected person's blood. Many people with HCV infection have no symptoms and are unaware of the need to seek treatment. Hepatitis C infects an estimated 150-200 million people worldwide.
Benitec Advances Hepatitis C Clinical Trial
1
Posted by HCV New Drugs
FILE UNDER HCV NEWS, TT-034
Benitec Advances Hepatitis C Clinical Trial
SYDNEY, Jan. 7, 2015 /PRNewswire/ -- Benitec Biopharma Limited (ASX: BLT, OTC: BTEBY) is pleased to advise that the third patient in its Phase I/IIa clinical trial of TT-034 for hepatitis C was dosed earlier today at the Duke Clinical Research Unit (USA). This is a significant step for this "first in man" study, and follows review of the collective data from the first two patients by the independent Data Safety Monitoring Board (DSMB). The DSMB determined that the patients from the first dosing cohort were clear of any significant treatment-related adverse events.
The newly dosed patient is the first to receive the increased dose of TT-034 (1.25 x 10^11 vg/kg, a concentration that is a half log higher than the doses administered in the first cohort). While TT-034 is designed as a potential "one-shot" cure for hepatitis C, the current dose is still below that expected to inhibit viral replication and data from the second dosing cohort are therefore expected to serve primarily as a further safety assessment.
As with previous patients, the newly dosed patient will be monitored for six weeks and results will be reviewed by the DSMB. Should the results indicate appropriate safety outcomes, the DSMB is expected to recommend that the remaining two patients in the second cohort be dosed. It is aimed to dose both at approximately the same time. The trial sites at Duke Clinical Research Unit and University of California San Diego have identified a number of patients who have passed initial screening who can be prepared in anticipation of this outcome.
About TT-034
TT-034 is a ddRNAi-based therapeutic, designed to treat and potentially cure hepatitis C (HCV) with a single administration. TT-034 targets the hepatitis C viral RNA at three separate, highly conserved sites. As such it acts as a "triple therapy" even though it is a monotherapy, and minimizes the ability of the virus to mutate and escape the therapy. Once it reaches the liver cells, it enters the nucleus and produces three separate short hairpin RNAs continuously for the lifetime of the cell. Thus TT-034 has the potential to not only treat the existing HCV infection, but also to guard against reinfection for months to years without the need to re-treat. TT-034 safety and efficacy has been tested extensively in pre-clinical in vivo studies with no adverse effects observed at therapeutic doses.
1
Posted by HCV New Drugs
FILE UNDER HCV NEWS, TT-034
Benitec Advances Hepatitis C Clinical Trial
SYDNEY, Jan. 7, 2015 /PRNewswire/ -- Benitec Biopharma Limited (ASX: BLT, OTC: BTEBY) is pleased to advise that the third patient in its Phase I/IIa clinical trial of TT-034 for hepatitis C was dosed earlier today at the Duke Clinical Research Unit (USA). This is a significant step for this "first in man" study, and follows review of the collective data from the first two patients by the independent Data Safety Monitoring Board (DSMB). The DSMB determined that the patients from the first dosing cohort were clear of any significant treatment-related adverse events.
The newly dosed patient is the first to receive the increased dose of TT-034 (1.25 x 10^11 vg/kg, a concentration that is a half log higher than the doses administered in the first cohort). While TT-034 is designed as a potential "one-shot" cure for hepatitis C, the current dose is still below that expected to inhibit viral replication and data from the second dosing cohort are therefore expected to serve primarily as a further safety assessment.
As with previous patients, the newly dosed patient will be monitored for six weeks and results will be reviewed by the DSMB. Should the results indicate appropriate safety outcomes, the DSMB is expected to recommend that the remaining two patients in the second cohort be dosed. It is aimed to dose both at approximately the same time. The trial sites at Duke Clinical Research Unit and University of California San Diego have identified a number of patients who have passed initial screening who can be prepared in anticipation of this outcome.
About TT-034
TT-034 is a ddRNAi-based therapeutic, designed to treat and potentially cure hepatitis C (HCV) with a single administration. TT-034 targets the hepatitis C viral RNA at three separate, highly conserved sites. As such it acts as a "triple therapy" even though it is a monotherapy, and minimizes the ability of the virus to mutate and escape the therapy. Once it reaches the liver cells, it enters the nucleus and produces three separate short hairpin RNAs continuously for the lifetime of the cell. Thus TT-034 has the potential to not only treat the existing HCV infection, but also to guard against reinfection for months to years without the need to re-treat. TT-034 safety and efficacy has been tested extensively in pre-clinical in vivo studies with no adverse effects observed at therapeutic doses.
Benitec is developing a breakthrough single dose cure for Hepatitis C which has commenced clinical trials.
Market
Hepatitis C virus (HCV) infects between 130 and 150 million people worldwide, and is the main cause of cirrhosis and hepatocellular carcinoma, which often result in liver transplant. There are 7 HCV genotypes, yet genotype 1 accounts for 75% of cases. The virus persists in the liver of 85% of those infected and, prior to July 2011, the Standard of Care (SoC) for genotype 1 was pegylated-interferon (peg-INF) and ribavirin (RBV) administered over 48 weeks. The SoC had a cure rate of 50-55% yet was associated with significant side effects including hematological, flu-like symptoms, and cognitive impairment.
Since July 2011, cure rates of up to 75% have been achieved by combining Specifically Targeted Antiviral Therapy (STAT-C) with peg-INF and RBV in double or triple therapies administered over long periods. However, a significant percentage of patients did not respond or withdrew due to side effects. A recent development is a single oral treatment without peg-INF or RBV which has higher cure rates and shortened treatment periods.
Rationale
Benitec has designed a ddRNAibased multi-cassette vector called TT-034, which targets 3 parts of the HCV genome with a single intravenous dose. TT-034 has achieved over 90% transfection of liver cells and, by targeting 3 separate, well-conserved regions of HCV simultaneously, it prevents generation of drug-resistant mutants, a major problem in the treatment of Hepatitis C. TT-034 is also designed to cause liver cells to continue to produce molecules that turn off replication of HCV, for as long as the liver cells persist, thus conferring protection from re-infection for months or potentially years, from a single dose.